The Cell Signaling Program provides a broad base of research into mechanisms of cell and molecular biology to facilitate discovery and validation of novel targets for cancer translational and clinical research. Targets involved in various fundamental processes may be utilized for cancer detection, diagnosis, prevention, and therapy as well as for monitoring efficacy of therapeutic interventions. Cell signaling encompasses multiple biochemical circuits in cells, including those involved in regulation of growth (size and synthesis), proliferation (duplication and division), stress responses and survival vs. apoptosis. The overall goals of this Program are to support outstanding research and emphasize the importance of understanding perturbations of signaling in cancer cells. Cell signaling proteins, especially receptors and protein kinases, are validated targets for development of therapies by pharmaceutical and biotechnology companies worldwide. The Cell Signaling Program is a resource for research on cancer composed of 31 members from 11 different departments within the University of Virginia, including 15 new members since the last renewal. It comprises a unique mix of faculty not replicated in any other activity at the University, drawing people from different departments in different schools within the University, and from various research Centers, who otherwise are isolated by administrative and organizational boundaries. We collaborate effectively with other Cancer Center Programs, providing expertise and knowledge to a variety of cancer-related projects. Over 25% of our 500 publications have been co-authored with members of other Programs and 10% were coauthored with members of this Program. This is a cancer-oriented group with $4.2M in NCI support, and $6.5M in other NIH grants and $11.6M in total peer-reviewed support. Research can be clustered into three thematic areas: 1) signal initiation by various types of cell-surface receptors, 2) signal transduction by GTP proteins and protein kinases and phosphatases and 3) chemical biology of small molecules that target specific proteins. This Program intends to tap our institutional strength in cell signaling research to close the circle of bedside-bench-bedside with discovery of novel targets, testing of small molecule inhibitors of those targets, and molecular assessments of therapies.